Tepmetko (tepotinib) / EMD Serono - LARVOL DELTA

Real-World Evidence for 10 Oncology Drugs Approved in the last 5 years: A Comprehensive Narrative Synthesis. (PubMed, Crit Rev Oncol Hematol) - "RWE confirms the effectiveness and safety of multiple recently approved oncology drugs reinforcing the external validity of RCTs."

HEOR • Journal • Real-world evidence • Review • Breast Cancer • Endometrial Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • ER • HER-2 • MSI

Phase II study of cabozantinib in patients with MET-altered lung cancers (ESMO 2023) - P2 | "Most pts (84%, 20/24) received a prior MET TKI (crizotinib, n=15; capmatinib, n=4; tepotinib, n=1); 16 pts (67%) and 13 pts (54%) received one or more prior lines of chemotherapy and immunotherapy, respectively...Due to its alternative type II binding mode, cabozantinib can be useful in the treatment of type I TKI resistance. As proof of concept, 3 of 4 responses were observed in patients with type I MET TKI progression."

Clinical • IO biomarker • P2 data • Lung Cancer • Oncology • Solid Tumor • MET

Targeting driver mutations in lung cancer with interstitial pneumonia: A nationwide study in Japan. (PubMed, Eur J Cancer) - "Multigene testing is underutilized in this population. While many targeted therapies carry a high risk of pneumonitis, sotorasib appeared relatively safe. Despite the risks, identifying and treating actionable oncogenic drivers may improve survival."

Journal • Fibrosis • Infectious Disease • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • BRAF • EGFR • KRAS • MET

Tepotinib in patients (pts) with METexon 14 (METex14) skipping non-small cell lung cancer (NSCLC) from the VISION study: ≥3-year follow-up outcomes (ELCC 2025) - P2 | "In VISION pts with ≥3-years follow-up, tepotinib continued to demonstrate robust and durable activity across treatment lines. Importantly, outcomes in pts with METex14 skipping were consistent with previous results, reinforcing tepotinib as a meaningful treatment option in this setting."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Tepotinib + osimertinib for EGFR mutant (EGFRm) NSCLC with MET amplification (METamp) after first-line (1L) osimertinib. (ASCO 2023) - P2 | "In this interim analysis of INSIGHT 2, tepotinib + osimertinib was highly active with durable responses, and was well tolerated in pts with EGFRm NSCLC with METamp after progression on 1L osimertinib. Tepotinib + osimertinib provides a potential chemotherapy-sparing oral targeted therapy option in this population with a high unmet need. Clinical trial information: NCT03940703."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Tepotinib + Osimertinib in EGFR-mutant NSCLC with MET Amplification Following 1L Osimertinib: INSIGHT 2 Primary Analysis (IASLC-WCLC 2023) - P2 | "Tepotinib + osimertinib demonstrated durable responses and a manageable safety profile in patients with EGFRm METamp NSCLC following 1L osimertinib, especially in Asian patients. Tepotinib + osimertinib provides a potential chemotherapy-sparing oral targeted therapy option in this population with a high unmet need."

Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • EGFR • MET

Tepotinib plus osimertinib in patients with EGFR-mutated non-small-cell lung cancer with MET amplification following progression on first-line osimertinib (INSIGHT 2): a multicentre, open-label, phase 2 trial. (PubMed, Lancet Oncol) - P2 | "Tepotinib plus osimertinib showed promising activity and acceptable safety in patients with EGFR-mutated NSCLC and MET amplification as a mechanism of resistance to first-line osimertinib, suggesting a potential chemotherapy-sparing oral targeted therapy option that should be further investigated."

Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR • MET

A tri-scale in silico framework integrating pharmacovigilance and mechanistic modeling suggests tepotinib-associated acute kidney injury risk. (PubMed, Ren Fail) - "Molecular docking revealed high-affinity binding between tepotiniband all six hub targets (Vina scores: -8.0 to -10.6 kcal/mol), providing a structural basis for the postulated mechanistic link to AKI. These findings not only highlight the necessity for enhanced renal monitoring in tepotinib-treated patients but, more broadly, establish the FAERS-NetDock Pipeline as a reusable, generalizable and hypothesis-generating framework for evaluating tyrosine kinase inhibitors (TKIs)-induced nephrotoxicity; this framework is immediately applicable to profiling the safety of other TKIs (e.g. crizotinib, capmatinib, savolitinib, afatinib and osimertinib) and is readily adaptable for de-risking a wider spectrum of targeted therapies."

Adverse events • Journal • Acute Kidney Injury • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • AKT1 • CASP3 • CDC37 • EGFR • HSP90AA1

Targeting Mesenchymal-Epidermal Transition (MET) Aberrations in Non-Small Cell Lung Cancer: Current Challenges and Therapeutic Advances. (PubMed, Cancers (Basel)) - "Encouragingly, several MET TKIs such as capmatinib, tepotinib, and savolitinib have been approved for the treatment of MET exon 14 skipping mutations. On 14 May 2025, the U.S. Food and Drug Administration granted accelerated approval to telisotuzumab vedotin-tllv for adult patients with locally advanced or metastatic non-squamous NSCLC whose tumors exhibit high c-Met protein overexpression and who have already received prior systemic therapy. In this review, we summarize the structure and physiological role of the MET receptor, the molecular mechanisms underlying aberrant MET activation, its contribution to acquired resistance against targeted therapies, and emerging strategies for effectively targeting MET alterations in NSCLC."

Journal • Review • Gastrointestinal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Tepotinib + osimertinib for EGFRm NSCLC with MET amplification (METamp) after progression on first-line (1L) osimertinib: Initial results from the INSIGHT 2 study (ESMO 2022) - P2 | "† Incomplete post-baseline assessments (n=2), SD <12 weeks (n=3), COVID-19-related early discontinuation (n=1), and PD/AE-related-early discontinuations (n=5). Conclusions In this initial analysis of INSIGHT 2, TEP+OSI was highly active and well tolerated in pts with EGFRm NSCLC with METamp after progression on 1L osimertinib and enables continuation of oral-only chemo-sparing therapy in this population with a high unmet need."

Clinical • Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Detection of MET amplification (METamp) in patients with EGFR mutant (m) NSCLC after first-line (1L) osimertinib. (ASCO 2023) - P2 | " During prescreening of the INSIGHT 2 study (NCT03940703) of tepotinib + osimertinib in post 1L osimertinib patients (pts) with EGFRm NSCLC, METamp was centrally assessed by TBx FISH (MET GCN ≥5 and/or MET/CEP7≥2) and/or by LBx NGS (MET plasma GCN ≥2.3; Archer). In this large comprehensive analysis, FISH+ METamp was detected in ~50% of pts progressing on 1L osimertinib, while L+ METamp was detected in only 11.7% of pts. METamp, which is the most common mechanism of resistance post 1L osimertinib, can frequently be undetected by using LBx NGS only. Given high specificity but low sensitivity of LBx, L+ pts can receive a MET TKI while a negative METamp result by LBx should be confirmed by FISH."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

LUNG-MAP SUB-STUDY: Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has a MET Exon 14 Skipping Gene Change (An Expanded Lung-MAP Treatment Trial) (clinicaltrials.gov) - P2 | N=56 | Recruiting | Sponsor: SWOG Cancer Research Network | Trial completion date: May 2029 ➔ May 2028

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • HER-2 • KRAS • MET • NTRK • RET • ROS1

Tepotinib-induced interstitial lung disease in a patient with adenosquamous lung carcinoma. (PubMed, Respir Med Case Rep) - "This case underscores the potential of early onset ILD with tepotinib, especially in patients with possible pre-existing ILD. Close monitoring and early intervention are essential, and further studies are needed to clarify the risk factors for MET-TKI-induced ILD."

Journal • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • MET

Clinical Activity of MET-TKIs in METex14 Skipping NSCLC With Poor Performance Status. (PubMed, Anticancer Res) - "MET-TKIs are effective for NSCLC with the METex14 skipping mutation; however, their efficacy for patients with a poor PS is limited."

IO biomarker • Journal • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Amivantamab in patients with NSCLC with MET exon 14 skipping mutation: Updated results from the CHRYSALIS study. (ASCO 2022) - P1 | "Median age was 70 y (range, 43-88), 58% were women, median prior lines of therapy was 2 (range, 0-10) [eg, crizotinib (n=13), capmatinib (n=11), tepotinib (n=5), anti-MET antibody (n=1)], and 23% had history of brain metastases at baseline. Amivantamab demonstrates anti-tumor activity in primary METex14 NSCLC including after prior MET inhibitor treatment. Enrollment is ongoing and updated data will be shown."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Health-related quality of life (HRQoL) with tepotinib in patients with MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC) with brain, liver, adrenal, or bone metastases in the phase II VISION trial. (ASCO 2024) - P2 | "In the VISION trial in METex14 skipping NSCLC, patients with brain, liver, adrenal or bone metastases maintained overall HRQoL during tepotinib treatment, with trends for improvement in cough, consistent with results for the overall population. 1. Mazieres et al."

Clinical • HEOR • P2 data • Cough • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Pulmonary Disease • Respiratory Diseases • Solid Tumor • MET

Long-term outcomes of tepotinib in patients with MET exon 14 skipping NSCLC from the VISION study. (ASCO 2023) - P2 | "The long-term outcomes of VISION demonstrate the robust and durable clinical activity of tepotinib, particularly in 1L T+ pts, and manageable safety profile, further defining its use in clinical practice. Clinical trial information: NCT02864992. >"

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Liquid and tissue biopsies for identifying MET exon 14 skipping NSCLC: Analyses from the Phase II VISION study of tepotinib. (PubMed, Clin Cancer Res) - "Tepotinib had robust, durable activity in TBx-positive/LBx-negative and TBx-positive/LBx-positive patients. While LBx is a complementary method to TBx for detecting METex14, it may preferentially select patients with higher tumor burden and poorer prognosis. Undetectable METex14 in baseline ctDNA (due to low ctDNA shedding) may define more favorable treatment outcomes."

Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Tepotinib in patients with non-small cell lung cancer with high-level MET amplification detected by liquid biopsy: VISION Cohort B. (PubMed, Cell Rep Med) - P2 | "Adverse events include edema (composite term; any grade: 58.3%; grade 3: 12.5%) and constipation (any grade: 41.7%; grade 3: 4.2%). Tepotinib provides antitumor activity in high-level METamp NSCLC (ClinicalTrials.gov: NCT02864992)."

Biopsy • Journal • Liquid biopsy • Constipation • Gastroenterology • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET • RB1

A phase II study of tepotinib in patients with advanced solid cancers harboring MET exon 14 skipping mutations or amplification (KCSG AL19-17). (PubMed, ESMO Open) - "Tepotinib demonstrated consistent antitumor activity in patients with METex14, and promising antitumor activity in various cancers with MET amplification. Detection of MET dysregulation by plasma NGS may predict the response to tepotinib."

Clinical • Journal • Metastases • P2 data • Anorexia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Randomized Trial of Tepotinib Plus Gefitinib Versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis. (PubMed, Clin Cancer Res) - "Final analysis of INSIGHT suggests improved PFS and OS with tepotinib plus gefitinib versus chemotherapy in a subgroup of patients with MET-amplified EGFR-mutant NSCLC, after progression on EGFR inhibitors."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Tepotinib Treatment in Patients With MET Exon 14-Skipping Non-Small Cell Lung Cancer: Long-term Follow-up of the VISION Phase 2 Nonrandomized Clinical Trial. (PubMed, JAMA Oncol) - P2 | "The findings from cohort C in this nonrandomized clinical trial supported the results from original cohort A. Overall, the long-term outcomes of VISION demonstrated robust and durable clinical activity following treatment with tepotinib, particularly in the treatment-naive setting, in the largest known clinical trial of patients with METex14-skipping NSCLC, supporting the global approvals of tepotinib and enabling clinicians to implement this therapeutic approach for such patients. ClinicalTrials.gov Identifier: NCT02864992"https://clinicaltrials.gov/ct2/show/NCT02864992"."

Clinical • Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Tepotinib in Patients with MET Exon 14 (METex14) Skipping NSCLC: Primary Analysis of the Confirmatory VISION Cohort C (IASLC-WCLC 2022) - "In VISION - the largest clinical trial of a MET inhibitor in METex14 skipping NSCLC - Cohort C primary analysis provided independent confirmation for robust and durable efficacy of tepotinib, with comparable or improved outcomes across endpoints compared to Cohort A. Efficacy was particularly durable in 1L T+ patients and promising intracranial activity was observed."

Clinical • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Tepotinib outcomes according to prior therapies in patients with MET exon 14 (METex14) skipping NSCLC (ESMO 2022) - P2 | "Treatment-related adverse events (TRAEs) occurred in 91.7% of pts (1L: 94.5%, ≥2L: 88.6%, prior IO: 90.1%); 34.2% had Grade ≥3 TRAEs (1L: 40.9%, ≥2L: 26.8%, prior IO: 27.2%) and 14.7% discontinued due to TRAEs (1L: 15.2%, ≥2L: 14.1%, prior IO: 17.3%). Table: 985P Conclusions In VISION – the largest study of a MET inhibitor in pts with METex14 skipping NSCLC – tepotinib demonstrated robust and durable efficacy irrespective of prior therapies and had a tolerable safety profile."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Clinical Response to Tepotinib According to Circulating Tumor (ct)DNA Biomarkers in Patients with Advanced/Metastatic NSCLC with High-level MET Amplification (METamp) Detected by Liquid Biopsy (LBx) (IASLC-NACLC 2022) - "Tepotinib showed meaningful activity, especially in first line, in the first trial of a MET inhibitor in EGFR WT NSCLC with high-level METamp to enroll based on a convenient LBx assay. Serial LBx could monitor molecular response and evaluate resistance."

Biomarker • Circulating tumor DNA • Clinical • Liquid biopsy • Constipation • Gastroenterology • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • MET • RB1